7DNF

DARPin 63_B7 in complex with V3-IY (MN) crown mimetic

7DNF の概要

• エントリーDOI: 10.2210/pdb7dnf/pdb
• 分子名称: DARPin 63_B7, V3-IY (MN) crown mimetic peptide, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: designed ankyrin repeat proteins, protein design, protein engineering, anti-hiv, de novo protein
• 由来する生物種: synthetic construct; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 78131.07

構造登録者

Wu, Y.,Plueckthun, A. (登録日: 2020-12-09, 公開日: 2021-12-15, 最終更新日: 2024-11-06)

主引用文献

Friedrich, N.,Stiegeler, E.,Glogl, M.,Lemmin, T.,Hansen, S.,Kadelka, C.,Wu, Y.,Ernst, P.,Maliqi, L.,Foulkes, C.,Morin, M.,Eroglu, M.,Liechti, T.,Ivan, B.,Reinberg, T.,Schaefer, J.V.,Karakus, U.,Ursprung, S.,Mann, A.,Rusert, P.,Kouyos, R.D.,Robinson, J.A.,Gunthard, H.F.,Pluckthun, A.,Trkola, A.
Distinct conformations of the HIV-1 V3 loop crown are targetable for broad neutralization.
Nat Commun, 12:6705-6705, 2021

PubMed Abstract: The V3 loop of the HIV-1 envelope (Env) protein elicits a vigorous, but largely non-neutralizing antibody response directed to the V3-crown, whereas rare broadly neutralizing antibodies (bnAbs) target the V3-base. Challenging this view, we present V3-crown directed broadly neutralizing Designed Ankyrin Repeat Proteins (bnDs) matching the breadth of V3-base bnAbs. While most bnAbs target prefusion Env, V3-crown bnDs bind open Env conformations triggered by CD4 engagement. BnDs achieve breadth by focusing on highly conserved residues that are accessible in two distinct V3 conformations, one of which resembles CCR5-bound V3. We further show that these V3-crown conformations can, in principle, be attacked by antibodies. Supporting this conclusion, analysis of antibody binding activity in the Swiss 4.5 K HIV-1 cohort (n = 4,281) revealed a co-evolution of V3-crown reactivities and neutralization breadth. Our results indicate a role of V3-crown responses and its conformational preferences in bnAb development to be considered in preventive and therapeutic approaches.

PubMed: 34795280
DOI: 10.1038/s41467-021-27075-0

実験手法

X-RAY DIFFRACTION (1.78 Å)